- This is the story of my evolution from a scientific skeptic
to a strong supporter for a specific "environmental" cause-the
phasing out of the chemical class called PBDEs in California due to their
negative impacts upon human development. PBDEs are used extensively as
a fire retardant in consumer products. This is a short story of one scientific
skeptic's conversion to become an advocate on this issue.
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- My skeptical tendency was driven by my negative experience
with those who tout scary cancer risk numbers from low-level radiation
exposure, without clarifying that such risks are purely hypothetical-having
never been shown in humans-and also ignoring the vast literature that shows
not only repair of low-level radiation damage, but actual reduction in
cancer risks following low-level radiation exposure (the hormesis effect).
Thus, I was skeptical of any claims about toxic effects at low doses of
a toxicant that are based merely on linear extrapolation from known high-dose
toxicity studies. As I learned, that was not the case with the PBDE issue.
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- Examining the Science: Low Doses Can Matter, Too
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- I got involved when Assemblywoman Wilma Chan requested
support for proposed PBDE phase-out legislation from the San Francisco
Medical Society in February of 2003.This request went to our board of directors,
an elected body of physicians of diverse specialties and practices. Some
scientific research was provided in support of the legislation, which I
reviewed prior to the board meeting. At the meeting, I expressed skepticism
about some of this research as applied to human health, particularly regarding
dose levels and putative effects on the developing fetus moderated by PBDE-related
thyroid hormone changes. As there was some uncertainty about how to proceed
with the endorsement request, I was deputized by the board to further review
the research and return with a recommendation regarding the legislation.
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- My initial review of the information in studies on rats
left me still skeptical that these effects were a likely risk for humans.
I was particularly focused on the thyroid hormone effects, since I deal
with clinical thyroid disease on an almost daily basis and considered it
an area in which I had significant expertise. I asked Steve Heilig of the
SFMS to get some more data and other opinions about my continued concerns.
Below is my original analysis of the paper by Zhou et al (Effects of short-term
in vivo exposure to polybrominated diphenyl ethers on thyroid hormones
and hepatic enzyme activities in weanling rats; Toxicological Science 61,
76-82, 2001):
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- "I labored through the paper this afternoon. It
clearly shows that the test dose crosses the placenta and stimulates liver
enzyme activity. I believe that the ability of the polybrominated test
compound to decrease T4 levels, but not T3 (the more metabolically active
thyroid hormone), at high dose levels is related to stimulation of enzymatic
conversion of T4 to T3 in the liver (which is where most of this conversion
occurs in people). It is likely from their data and discussion that these
compounds do not affect the thyroid gland of either the mother or the fetus
in any direct manner. As long as normal levels of T3 are maintained, there
should not be any thyroid-related developmental abnormalities, as I am
unaware of any action of thyroid hormone that are specific to T4."
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- Steve Heilig then sent my comments and continuing concerns
out for input and advice to a network of environmental researchers working
on the PBDE issue. Dr. Susan Lee was the first to respond with a reference
to answer my specific question. In her response, she stated, "I have
to respectfully disagree with your comments. Maternal hypothyroxinemia
(low maternal T4) is associated with adverse development of the fetal brain.
I direct you to an excellent review of the topic (Morreale de Escobar et
al; Clinical perspective: Is neuropsychological development related to
maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol
Metab 85(11): 2000;3975-3987). For example, the researchers conclude that
'normal maternal T3 concentrations do not seem to prevent the potential
damage of a low supply of T4 . . .' I am not sure of the mechanism of this
phenomenon."
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- At my request, Steve located and downloaded the full
article from the Internet for my review. After studying it in detail I
concluded the following:
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- "This is a very good article full of experimental,
epidemiological and sound theoretical information that supports the idea
that maternal T4 is itself very important for the very earliest and likely
most important phase of fetal brain development. This process probably
requires the T3 to be generated in those brain tissues from that maternal
T4 and this need is not met by circulating T3 that is available in the
fetal brain tissue. Fascinating. Live and learn. This is a very clear answer
to my big concern about the thyroid hormone impacts on fetal brain development.
This validates the concern about PBDE effects via lowering T4 levels selectively.
. .Our review of this single topic was very valuable for me because it
is a great example of how complex and subtle the changes may be that can
cause damage in the fetus. It is a level of complexity and subtlety that
is usually below my radar screen as a practicing clinician."
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- Thus, by pursuing each question with an open mind and
a willingness to dig deeper for answers, I became a strong convert to the
dangers of PBDEs and the need to decrease exposure in the human population.
At my recommendation, the SFMS Board of Directors endorsed the legislation
to ban PBDEs in California. It passed and became California law. The Value
of an Open Mind
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- As physicians we are trained to be cautious and skeptical
about new research, especially new research that appears to stretch or
contradict established scientific theory or clinical knowledge. But we
need to keep an open mind about even the information we hold most sacred
and always cast a critical eye on our assumptions and the positions we
hold based on those assumptions.
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- An open mind and healthy skepticism are, in my opinion,
the very essence of the scientific method. These qualities also carry the
force of history, as our knowledge continues to dethrone one after another
of the "absolute truths" we used to hold so certain. The story
of my conversion from skeptic to ardent supporter of the ban on PBDEs is
an example of the importance of applying the scientific method with an
open mind and a degree of humility about strongly held beliefs. In the
process, I gained new knowledge about thyroid hormone in early fetal development.
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- I call on all who read this to maintain an attitude that
continually questions even your most sancrosanct beliefs and truths. We
must all adopt a willingness to abandon even our core assumptions when
new data is revealed. With such an attitude, even the most skeptical individuals
can be converted into powerful and rational advocates.
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- - Dr. Lull is a past president of the San Francisco Medical
Society, chief of nuclear medicine, at San Francisco General Hospital,
clinical professor of radiology and laboratory medicine at UCSF, and director
of the nuclear medicine residency program at UCSF.
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- http://www.sfms.org/sfm/sfm404f.htm
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